2019年6月
Macrocyclic peptide-based inhibition and imaging of hepatocyte growth factor.
Nature chemical biology
- 巻
- 15
- 号
- 6
- 開始ページ
- 598
- 終了ページ
- 606
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41589-019-0285-7
- 出版者・発行元
- NATURE PUBLISHING GROUP
Activation of hepatocyte growth factor (HGF) by proteolytic processing is triggered in cancer microenvironments, and subsequent signaling through the MET receptor is involved in cancer progression. However, the structure of HGF remains elusive, and few small/medium-sized molecules can modulate HGF. Here, we identified HiP-8, a macrocyclic peptide consisting of 12 amino acids, which selectively recognizes active HGF. Biochemical analysis and real-time single-molecule imaging by high-speed atomic force microscopy demonstrated that HiP-8 restricted the dynamic domains of HGF into static closed conformations, resulting in allosteric inhibition. Positron emission tomography using HiP-8 as a radiotracer enabled noninvasive visualization and simultaneous inhibition of HGF-MET activation status in tumors in a mouse model. Our results illustrate the conformational change in proteolytic activation of HGF and its detection and inhibition by a macrocyclic peptide, which may be useful for diagnosis and treatment of cancers.
- リンク情報
- ID情報
-
- DOI : 10.1038/s41589-019-0285-7
- ISSN : 1552-4450
- eISSN : 1552-4469
- PubMed ID : 31101918
- Web of Science ID : WOS:000468195600013